AB0185 PHENOTYPES OF DRUG-FREE RHEUMATOID ARTHRITIS FLARE AND IMPACT OF RESIDUAL SUBCLINICAL ECOGRAPHIC JOINT INJURY IN ACPA POSITIVE AND ACPA NEGATIVE DISEASE
Authors: E. Bozzalla Cassione, S. Grignaschi, B. Xoxi, M. I. Greco, T. Luvaro, I. Mazzucchelli, S. Bugatti, C. Montecucco, A. Manzo
Journal: Annals of the Rheumatic Diseases (2022)

Background The mechanisms of flare across the pathogenic spectrum of RA remain unclear. To what extent RA flare reproduces the dynamics of disease onset or is primarily driven by new dynamics is not known. Furthermore, the hypothesis of a role for circulating auto-antibodies in determining different mechanism behind flare has never been challenged. Objectives To evaluate whether RA flare after remission achievement reproduces the phenotype of onset or it is characterized by a different phenotype primarily driven by the pattern of residual joint injury after treatment, in ACPA positive and negative patients. Methods 53 RA patients, in stable drug-free remission (DFR) after early csDMARDS introduction and displaying clinical flare across 60 months of follow-up were analysed for clinical, laboratory and ultrasound (US) characteristics at diagnosis, treatment discontinuation, and flare (DAS28- and/or physician-based flare). We compared the synovitis clinical phenotype (ACR 1987 criteria defined districts), PROs and the inflammatory status at disease flare versus onset. We then measured the impact of residual subclinical US joint injury (absence of objective synovitis and GS&gt;1 and/or PD&gt;0) at the time of drug discontinuation, on the synovitis clinical phenotype of flare. Finally, we explored differences in the outcomes in ACPA positive and negative RA. Results Cohort characteristics are shown in Table 1. As inferred by paired analyses, no significant differences were observed between onset and flare concerning composite indices of disease activity, and subjective/semi-objective domains. However, flare appeared to be significantly less inflammatory in terms of CRP, ESR, SJC, morning stiffness and HAQ (p&lt;0.05). These differences remained after adjustment for diagnostic delay including only very early RA patients (&lt;3 months from symptoms’ onset). The evaluation of the frequency of articular districts’ involvement revealed no difference between onset and flare both for SJC and TJC (Figure 1). However, the percentage of SJs at flare being present at onset showed a high variability among patients. Stratification for ACPA status demonstrated a significantly higher recurrence of synovitis in joints involved at onset in ACPA negative vs ACPA positive patients (p&lt;0.05). The percentage of SJs at flare presenting residual subclincal US injury at the time of drug discontinuation was significantly higher in ACPA negative vs ACPA positive patients (p&lt;0.05) and negatively correlates with the ACPA titer (R 0.354, p&gt;0.05). Table 1. Comparison between Onset and Flare Onset,median (IQR) Flare,median (IQR) Sex, female (%) 34 (64) \ Age at Symptoms onset (yrs) 57 (43-65) \ Diagnostic delay(months) 3 (2-7) 1.5 (1-2) * ESR (mm/h) 20.0 (12.0-38.5) 17 (9.00-27.0)§ CRP (mg/dL) 0.640 (0.307-2.11) 0.370 (0.220-1.05) *§ HAQ 0.625 (0.375-1.13) 0.438 (0.125-0.875) GH 40.0 (26.5-50.0) 40 (30.0-50.0) PGA 50.0 (27.0-66.5) 49 (20.0-70.0) EGA 38.0 (27.0-60.0) 40 (30.0-60.0) SJC/66 7 (4.00-10.0) 4 (3.00-6.00) *§ TJC/68 5 (2.00-10.0) 5 (2.00-11.0) DAS28-ESR 4.55 (3.29-5.36) 3.98 (3.56-4.61) DAS28-CRP 3.98 (3.08-4.88) 3.83 (3.00-4.27) Morning Stiffness (minutes) 60.0 (11.3-90.0) 10 (1.00-30.0) *§ Index: *significant compared to onset, § significant compared to onset considering only VERA Conclusion RA flare in patients achieving DFR seems to be less severe in terms of inflammatory markers and synovitis recurrence, despite a similar degree of joint tenderness and patients’ perception compared to disease onset. The arthritis phenotype undergoes detectable changes more in ACPA positive than negative patients. The residual subclinical US joint damage seems to drive the localization of synovitis recurrence in ACPA negative more than positive patients, supporting the existence of pathologic differences in the process of disease reactivation in the two groups. Disclosure of Interests None declared